The Epidemiology Project of the UC Davis Center for Children's Environmental Health (CCEH), will, in the[unreadable] second funding period, build upon our discovery of immunologicand molecular biomarkers specific to[unreadable] children with autism found in 2-5 year olds enrolled in the CHARGE (Childhood Autism Risks from Genetics[unreadable] and Environment) Study. First, newborn blood spots from children in each of three groups (i.e., autism,[unreadable] developmental delay, and general population controls) will be analyzed in Project 2 for a variety of immune[unreadable] biomarkers and in Core 3 (Analytical Chemistry) for metal concentrations. The data obtained from newborn[unreadable] bloodspots, when compared to data we have already collected from the same individuals in early childhood,[unreadable] will provide important information for the period shortly before birth about immune dysfunction and metal[unreadable] exposures or metabolism in children who are later diagnosed with autism. In other words, we will extend our[unreadable] investigation of post-diagnosis differences to the pre-diagnostic period. The hypothesis we will test is that[unreadable] children with autism can be distinguished from those without autism by markers of immune dysregulation (at[unreadable] birth, as well as post-diagnosis) and by prenatal, immunologically relevant events and exposures. Second,[unreadable] in collaboration with Core 3, we will determine if children with and without autism differ with regard to[unreadable] exposures, body burdens, and excretion of xenobiotics, including metals, pesticides and PBOE's. Exposures[unreadable] are based on questionnaire information and environmental databases covering toxic emissions, hazardous[unreadable] air pollutants and pesticide applications. Body burdens are measured in blood or plasma, and excretion is[unreadable] evaluated in hair or urine; these measurements are performed in the Core 3 laboratories. Third, we will test[unreadable] the hypothesis that transcriptional genomic profiles of children with autism differ from those of children[unreadable] without autism. Particular attention will be placed on genes related to biotic and xenobiotic metabolism.[unreadable] Fourth, Projects 1 and 2 in collaboration with the COTC (Core 2) will collect a second set of blood samples[unreadable] from 375 children who enrolled in the CHARGE study in the first project period. This study (CHARGE-BACK)[unreadable] will examine stability overtime in the immune cell markers that were determined when these children were 2-[unreadable] 5 years old. CHARGE-BACK blood samples will provide peripheral immune cells to study how autism alters[unreadable] properties of cell activation, and susceptibility to known immunotoxicants (Project 2 and Core 4). Fifth,[unreadable] Project 1 will launch a new cohort study that tracks 200 women at high risk of giving birth to a child who[unreadable] develops autism, starting from early pregnancy and following the pregnancies and the babies to the age of[unreadable] three years. This new cohort study is called Markers of Autism Risk in Babies - Learning Early Signs[unreadable] (MARBLES). Fieldwork for the MARBLES study will be tightly integrated with the COTC (Core 2) efforts, and[unreadable] the specimens will be evaluated in Cores 3 and 4, and in Project 2. The goal is to determine early predictors[unreadable] of autism, whether they be immunologic, genomic, or environmental.